This project concentrates on transfer RNAs and their specific interactions with proteins. Attempts will be made to detect a transient covalent bond in aminoacyl tRNA synthetase-tRNA complexes. Preliminary experiments have suggested that such bonds may form, and a variety of further experiments will explore this issue in more depth. In addition, as a follow-up on earlier promising results, oligonucleotides with sequences corresponding to sections in a tRNA where a transient bond may form will be tested out as inhibitors of synthetases. Photo-cross-linking studies will be continued, with the aim of locating on a synthetase the nucleic acid contact sites. Together with x-ray crystallographic studies, it may be possible to use the cross-linking data to construct a molecular model for a synthetase-tRNA complex. Much evidence has suggested tRNAs participate in many processes other than protein synthesis. Some of those processes may involve protein-nucleic acid complexes. These questions will be studied by attempting to isolate proteins other than a synthetase which bind specifically to a particular tRNA. Affinity chromatography methods will be used. In addition, the physiological significance of these systems will be explored.